Norovirus (NoV) is a non-enveloped virus that belongs to the family Caliciviridae. It constitutes the mayor cause of epidemic gastroenteritis in close settings (Green, Caliciviridae: The Noroviruses. Fields Virology, 6th edition. H. P. Knipe, et al. (eds), published by Philadelphia: Lippincott Williams & Wilkins: 582-608, (ISBN-13: 978-1451105636), 2013) and since the introduction of rotavirus vaccines, norovirus has become the leading cause of medically attended acute gastroenteritis in U.S. children, associated with nearly 1 million health care visits annually (Payne, et al., N Engl J Med 368(12): 1121-30, 2013). A gastroenteritis episode due to NoV is incapacitating during the acute phase that usually lasts from 1 to 3 days and includes explosive vomiting, stomach cramps and diarrhea Immunocompetent patients usually recover completely from the illness but the gastroenteritis may be severe in young children, the elderly and immunocompromised, increasing the risk for morbidity and mortality (Kaufman et al., Antiviral Res 105C: 80-91, 2014). It was estimated that around 200,000 children die annually because of NoV gastroenteritis, especially in developing countries (Patel et al., Emerg Infect Dis 14(8): 1224-3, 2008; Patel et al., J Clin Virol 44(1):1-8, 2009). In immunocompromised patients, NoV is recognized as an important cause of chronic gastroenteritis, with long-term virus shedding and increased morbidity in this population (Ludwig, et al., J Med Virol 80(8): 1461-7, 2008; Henke-Gendo et al., J Clin Microbiol 47(9): 2855-62, 2009; Florescu et al., Pediatr Transplant 15(7): 718-21, 2011). In immunocompetent patients the virus shedding after infection lasts for approximately 30 days, while in immunocompromised patients virus shedding has been detected for up to 3 years (Bok and Green, N Engl J Med 367(22): 2126-32, 2012; Payne et al., N Engl J Med 368(12): 1121-30, 2013; Kirby et al., J Med Virol, PubMed PMID: 24531909, 2014). It has been proposed that long term virus shedding may contribute to the spread of the virus (Debbink et al., PLoS Pathog 8(10): e1002921, 2014; Debbink et al., J Virol., Mar. 19, 2014).
The NoV genome is composed of a single-stranded positive-sense RNA molecule that contains three open reading frames. The genome is surrounded by a non-enveloped capsid composed of the major capsid protein, VP1, encoded by ORF2, and a minor structural protein, VP2, encoded by ORF3 (Green, Caliciviridae: The Noroviruses, Fields Virology, 6th edition Knipe et al. (eds), published by Philadelphia: Lippincott Williams & Wilkins: 582-608, (ISBN-13: 978-1451105636), 2013). Crystallographic analysis showed that the NoV capsid is formed by 180 molecules of VP1, organized into 90 dimers. Each VP1 monomer is divided into two domains designated shell (S) and protruding (P), linked by a flexible hinge. The P domain is further divided into P1 and P2 subdomains, with P2 as the outermost domain exposed on the surface (Prasad et al., Science 286(5438): 287-90, 1999).
Noroviruses are divided into six major genogroups designated Genogroup (G)I through GVI. GI and GII contain the majority of NoV strains associated with human disease and are further divided into 9 and 21 genotypes, respectively (Kroneman et al., Arch Virol 158(10): 2059-68, 2013). The NoV GI.1 was the first genotype described, the GII.4 genotype has been associated with the majority of global outbreaks since the mid-1990s, when active surveillance with molecular diagnostic techniques was initiated (Zakikhany et al., PLoS One 7(7): e41625, 2012; Zheng et al., Virology 346(2): 312-23, 2006; Allen et al., Virol J 6: 150, 2009; Bok et al., J Virol 83(22): 11890-901, 2009; Patel et al., J Clin Virol 44(1): 1-8, 2009; Lindesmith et al., J Virol 85(1): 231-42, 2011; Lindesmith et al., J Virol 87(5): 2803-13, 2013). A need remains for reagents that can be used to detect and treat NoV infections.